Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

Abstract

Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 ؎ 3 years versus 48 ؎ 1 years, P ‫؍‬ 0.0008), had higher serum levels of bilirubin at accession (4.1 ؎ 0.9 mg/dL versus 2.3 ؎ 0.2 mg/dL, P ‫؍‬ 0.02), presented acutely more frequently (43% versus 14%, P ‫؍‬ 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P ‫؍‬ 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission (16 ؎ 1 versus 10 ؎ 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. Conclusion: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome. (HEPATOLOGY 2007;46:1138-1145

Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs

“…Corticosteroid treatment is by itself a cause for obesity, diabetes and fatty liver, and worsening liver tests during treatment may not be a call for more corticosteroids. 7 Lastly, in younger patients,…”

“…of patients with autoimmune hepatitis fail to respond to conventional therapy, [6][7][8] and these patients can progress to cirrhosis, develop hepatocellular carcinoma, require liver transplantation, or die more from liver failure with mortality rates of approximately 30%. 7 HLA DRB1*03 10 and lack of improvement in laboratory indices within 1-2 weeks of corticosteroid treatment identify individuals with a high risk for treatment failure.…”

“…7 HLA DRB1*03 10 and lack of improvement in laboratory indices within 1-2 weeks of corticosteroid treatment identify individuals with a high risk for treatment failure. 6,8,13 Inability to improve the MELD, MELD plus sodium, or the United Kingdom end-stage liver disease (UKELD) scores within 7 days of corticosteroid treatment predict a poor outcome for treatmentnaïve, jaundiced individuals with a sensitivity of 85% and specificity of 68%.…”

Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis

“…Clinical experiences have now recognised that the rapidity 18 and completeness [259][260][261] of the response to conventional therapy are important factors in preventing or reducing hepatic fibrosis in autoimmune hepatitis. Slow responders and refractory patients have been described, 98,262 and non-invasive laboratory and radiological methods are now available to better monitor the fibrotic process. 157,166,193,263 Individualised modifications in conventional treatment may be beneficial, 16 and promising anti-fibrotic therapies that can supplement treatment must be evaluated and incorporated if validated.…”

Treatment of autoimmune liver disease: current and future therapeutic options

“…Follow-up biopsies should however be considered given that 5% of patients per year develop cirrhosis, a rate much higher in those with ongoing inflammation. Moreover, relapse and progression to fibrosis are almost universal when immunosuppression is stopped in the presence of residual interface hepatitis [Carpenter and Czaja, 2002;Montano-Loza et al 2007b;Czaja and Carpenter, 2003]. The combination of normal IgG and transaminase levels together correlates with lower histological inflammatory scores (Knodell index <4) [Lüth et al 2008] in around 90% of cases, although histological remission may lag 3-6 months behind biochemical remission.…”